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Background: The mTOR signaling pathway is inactivated by AMPK’s tumor-suppressing function. It is recognized that ubiquitin conjugating enzyme 2O (UBE2O), which directly targets AMPK for ubiquitination and degradation, is intensified in human cancers. Methods: This study investigated the clinical data about prostate cancer. Examination was also carried out into tissue microarrays (TMA) of human prostate cancer (n = 382) and adjacent non-neoplastic tissues around prostate cancer (n = 61). The TMA slides were incubated with antibodies against UBE2O, and the cores were scored by the pathologist blind to cancer results. Results: Very strong positive correlations were identified between the expression of UBE2O staining and high PSA and pathological stage of prostate cancer. Cox’s proportional hazard analysis established correlations between the following: (1) positive surgical margin and biochemical recurrence free survival, (2) PSA grade and clinical recurrence free survival, (3) regional lymph node positive and clinical recurrence free survival, (4) adjuvant treatment and overall survival, and (5) pathological T stage and overall survival. Conclusion: There is a positive correlation between the expression of UBE2O staining and prognosis for prostate cancer. Thus, a prostate cancer prognosis can be assessed with the expression of UBE2O staining.

Purpose – This research examines the relationship between motivational factor in regards to writing comments and tourist attitude. Specifically, the study (a) explains the relationships between motivational factors and tourist recommendation intentions on SNSs, and (b) evaluates the factors influencing recommendation intentions on SNSs. Design – To develop a useful marketing strategy in the Social Networking Site (SNS) environment in Korea tourism, it is important to identify the relationship between the motivational factors regarding the reasons for writing comments and tourist attitude to suggest effective tourism marketing on SNSs due to the growing interest in Korea tourism among Chinese students and tourists. Methodology – The measurement items were adapted for an SNS setting from published studies related to the hospitality and tourism field. All of the measurement items were based on a 7-point Likert-type scale. Finding – The results offer valuable suggestions to SNS firms and marketers with important insights into the quality of SNS contents for developing marketing strategies. Originality – For further utilization as an effective bridging tool between SNS users, more detailed understanding of the developed approach for using SNSs is provided.

Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS. After subcellular fractionation of motor neuron-like cell lines expressing wild-type or G93A mutant hSOD1, quantitative mass spectrometry and next-generation RNA sequencing (RNA-seq) were performed for the nuclear and cytoplasmic compartments. A subset of the results was validated via immunoblotting. A total of 1,925 proteins were identified in either the nuclear or cytoplasmic fractions, and 32% of these proteins were quantified in both fractions. The nucleocytoplasmic distribution of 37 proteins was significantly changed in mutant cells with nuclear and cytoplasmic shifts in 13 and 24 proteins, respectively (p

Purpose: To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections. Materials and Methods: Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization. Results: In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling. Conclusions: Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Hydroxycholesterols (OHCs), metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We aimed to develop a sensitive and reliable method for the quantitative analysis of three major OHCs (24S-, 25-, and 27-OHCs), and to evaluate their concentration in the cerebrospinal fluid (CSF) and serum of patients with NMO. The levels of the three OHCs in the serum and CSF were measured using liquid chromatography-silver ion coordination ionspray tandem mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry with picolinyl ester derivatization, respectively. The linear range was 5-250 ng/mL for 24S- and 27-OHC, and 0.5-25 ng/mL for 25-OHC in serum, and was 0.1-5 ng/mL for 24S- and 27-OHC, and 0.03-1 ng/mL for 25-OHC in CSF. Precision and accuracy were 0.5%-14.7% and 92.5%-109.7%, respectively, in serum, and were 0.8%-7.7% and 94.5%-119.2%, respectively, in CSF. Extraction recovery was 82.7%-90.7% in serum and 68.4%-105.0% in CSF. When analyzed in 26 NMO patients and 23 control patients, the 25-OHC (0.54 ± 0.96 ng/mL vs. 0.09 ± 0.04 ng/mL, p = 0.032) and 27-OHC (2.68 ± 3.18 ng/mL vs. 0.68 ± 0.25 ng/mL, p = 0.005) were increased in the CSF from NMO patients. When we measured the OHCCSF index that controls the effects of blood-brain barrier disruption on the level of OHC in the CSF, the 27-OHCCSF index was associated with disability (0.723; 95% confidence interval (CI)- 0.181, 0.620; p = 0.002), while the 24-OHCCSF index (0.518; 95% CI- 1.070, 38.121; p = 0.040) and 25-OHCCSF index (0.677; 95% CI- 4.313, 18.532; p = 0.004) were associated with the number of white blood cells in the CSF of NMO patients. Our results imply that OHCs in the CNS could play a role in the pathogenesis of NMO.

BackgroundPatients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.ObjectiveTo evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.MethodsSixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.ResultsCompared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.ConclusionsChronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.

BACKGROUND AND OBJECTIVE: Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system with a relapsing and remitting course. We aimed to identify factors associated with the time to next attack, including the effect of the natural disease course and the diverse treatment regimens, by applying a longitudinal statistical analysis to the individual attacks of each patient. METHODS: In total, 184 acute attacks among 58 patients with either NMO or NMO spectrum disorder with anti-aquaporin-4 antibody were assessed retrospectively. Patient demographics, clinical characteristics at each attack, and type of treatment during inter-attack periods were assessed. The dependent variable was defined as the time from each attack to the next attack (inter-attack interval). An exponential accelerated failure time model with shared gamma frailty was adapted for statistical analysis. RESULTS: A multivariable analysis revealed that the time from each attack to the next attack in NMO increased independently by 1.31 times (95% confidence interval (CI), 1.02-1.67; p = 0.035) with each additional cumulative attack experienced, by 5.34 times (95% CI, 1.57-18.13; p = 0.007) with combined azathioprine treatment and continued oral prednisolone, and by 4.26 times (95% CI, 1.09-16.61; p = 0.037) with rituximab treatment. CONCLUSION: The time to next attack in NMO can increase naturally in the later stages of the disease as the number of cumulative attacks increases. Nevertheless, both combined azathioprine treatment with continued oral prednisolone and rituximab treatment were also associated with a longer time to next attack, independently of the natural disease course of NMO.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2

OBJECTIVE: To demonstrate that hypolipidemia is a typical feature of the mouse model of amyotrophic lateral sclerosis (ALS) and to assess the association between hypolipidemia and disease stage, dietary intake, and sex. METHODS: We compared daily dietary intake, body weight, and serumlipid and glucose levels in ALS mice and wild-type controls at different stages of the disease. FINDINGS: Total cholesterol low-density lipoprotein (LDL) and LDL/high-density lipoprotein (HDL) ratio were significantly lower in ALS mice compared with controls. Subgroup analysis revealed that the incidence of hypolipidemia was significantly greater in male, but not female, ALS mice compared with control mice and that hypolipidemia was present at the presymptomatic stage of the disease. This hypolipidemia can be found without a decrease in the serum levels of other energy sources, such as glucose, in the presymptomatic stage. CONCLUSIONS: Hypolipidemia is present at the presymptomatic stage of the ALS mouse model in the absence of malnutrition, significant neuromuscular degeneration or regeneration, and respiratory difficulty. Our findings suggest that hypolipidemia might be associated with the pathomechanism of ALS and/or lipid-specific metabolism rather than simply an epiphenomenon of neuromuscular degeneration or energy imbalance.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) suffer from hypoventilation, which can easily worsen during sleep. This study evaluated the efficacy of capnography monitoring in patients with ALS for assessing nocturnal hypoventilation and predicting good compliance with subsequent noninvasive ventilation (NIV) treatment. METHODS: Nocturnal monitoring and brief wake screening by capnography/pulse oximetry, functional scores, and other respiratory signs were assessed in 26 patients with ALS. Twenty-one of these patients were treated with NIV and had their treatment compliance evaluated. RESULTS: Nocturnal capnography values were reliable and strongly correlated with the patients' respiratory symptoms (R(2) = 0.211-0.305, p = 0.004-0.021). The duration of nocturnal hypercapnea obtained by capnography exhibited a significant predictive power for good compliance with subsequent NIV treatment, with an area-under-the-curve value of 0.846 (p = 0.018). In contrast, no significant predictive values for nocturnal pulse oximetry or functional scores for nocturnal hypoventilation were found. Brief waking supine capnography was also useful as a screening tool before routine nocturnal capnography monitoring. CONCLUSION: Capnography is an efficient tool for assessing nocturnal hypoventilation and predicting good compliance with subsequent NIV treatment of ALS patients, and may prove useful as an adjunctive tool for assessing the need for NIV treatment in these patients.

Since the identification of the human urinary microbiome, numerous studies have characterized this microbial community and improved our knowledge of its association with urinary diseases. This association between urinary diseases and microbiota is not confined to the urinary microbiota; it is interconnected with the microbiota of other organs. The gastrointestinal, vaginal, kidney, and bladder microbiota all affect urinary diseases because they work with their respective organs to control the growth and operation of the immune, metabolic, and nervous systems through dynamic bidirectional communication along the bladder-centered axis. Therefore, disturbances in the microbial communities may result in the emergence of urinary diseases. In this review, we describe the increasing and intriguing evidence of complicated and critical relationships that may contribute to the development and progression of urinary diseases through disruption of the microbiota in various organs.

Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. Methods: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient’s age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. Results: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. Conclusions: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

Our knowledge that “urine is sterile” is no longer accepted after the development of a next-generation sequencing (NGS) test. Using NGS, microbiota in the human body were discovered, and it is expected that this will improve our understanding of human diseases. However, the mechanism involved in the effect of the microbiome on diseases is still poorly understood. Associations of gut microbiome with diseases have been recently reported. Based on such associations, bladder–gut–brain axis, gut–bladder axis, gut–vagina–bladder axis, and gut–kidney axis as novel mechanisms of action of the microbiome have been suggested. Each axis can influence the development and progression of disease through interactions. In these interactions, metabolites of the microbiome including short-chain fatty acids (SCFA) and the inflammasome play an important role. Inflammasomes are multiprotein oligomers that can initiate inflammatory responses. Inflammasomes can trigger inflammation and pyroptosis and ultimately contribute to disease development. SCFAs play an important role in immune cell migration, cytokine production, and maintenance of cellular homeostasis. Associations of inflammasomes with systemic diseases such as obesity and insulin resistance have been reported. The roles of inflammasomes and SCFAs in kidney, bladder, and prostate diseases have also been revealed recently.